Differential X chromosome inactivation patterns during the propagation of human induced pluripotent stem cells

Tomoko Andoh-Noda, Wado Akamatsu, Kunio Miyake, Tetsuro Kobayashi, Manabu Ohyama, Hiroshi Kurosawa, Takeo Kubota, Hideyuki Okano

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Human induced pluripotent stem cells (hiPSCs) represent a potentially useful tool for studying te molecular mechanisms of disease thanks to their ability to generate patient-specific hiPSC clones. However, previous studies have reported that DNA methylation profiles, including those for imprinted genes, may change during passaging of hiPSCs. This is particularly problematic for hiPSC models of X-linked disease, because unstable X chromosome inactivation status may affect the detection of phenotypes. In the present study, we examined the epigenetic status of hiPSCs derived from patients with Rett syndrome, an X-linked disease, during long-term culture. To analyze X chromosome inactivation, we used a methylation-specific polymerase chain reaction (MSP) to assay the human androgen receptor locus (HUMARA). We found that single cell-derived hiPSC clones exhibit various states of X chromosome inactivation immediately after clonal isolation, even when established simultaneously from a single donor. X chromosome inactivation states remain variable in hiPSC clones at early passages, and this variability may affect cellular phenotypes characteristic of X-linked diseases. Careful evaluation of X chromosome inactivation in hiPSC clones, particularly in early passages, by methods such as HUMARA-MSP, is therefore important when using patient-specific hiPSCs to model X-linked disease.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalKeio Journal of Medicine
Volume66
Issue number1
DOIs
Publication statusPublished - 2017

Keywords

  • Epigenetic memory
  • Induced pluripotent stem cells
  • Reprogramming
  • Rett syndrome
  • X chromosome inactivation

ASJC Scopus subject areas

  • Medicine(all)

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